Antiandrogens are receiving increasing attention as new therapeutic agents in the treatment of human benign prostatic hypertrophy and prostatic adenocarcinoma. Anti-androgens have also been used in our laboratory as tools to elucidate the temporal requirements of androgens during cell cycle phases of prostatic growth. This proposal will encompass the following topics: I. A method for evaluating antiandrogens will be developed based on their comparative effectiveness in preventing the marked increase in prostatic DNA synthesis occurring at 72 hours following androgen administration to castrate rats. II. To expand the use of antiandrogens in our present studies on the temporal requirements of androgens in the prostatic nucleus at various phases of the cell cycle in relation to protein, RNA and DNA synthesis. III. Testosterone is required in the male in the neonate period (days 1-5), to "mark" the prostate for later response to androgens at puberty. We have confirmed this and observed, in addition, that this marking is not antagonized by antiandrogens. This mechanism will be studied in more detail. IV. We have observed that only one specific androgen glucuronide conjugate (5 alpha-androstanediol) is formed directly in the sex accessory tissues of the rat and this formation may be antagonized in vitro by antiandrogens. In contrast, a different single androgen glucuronide (5 alpha-dihydrotestosterone) is formed directly in human benign prostatic hypertrophy. The glucuronide patterns and the role of antiandrogens in suppressing their formation will be compared in normal and abnormal human prostatic tissues.